H3D has a dedicated parasitology team to perform blood stage screening for malaria with access to other lifecycle stages through our partnerships. The malaria biology team have developed various enzymatic assays as well as an in vivo mouse model.
See the table below for additional details, including average turnaround time and control(s). For assays where an average turnaround time/control(s) are not available, this indicates that turnaround time is dependent on your unique experimental design and conditions; please book a consultation for an estimated turnaround time or additional information.
H3D's expertise and experience is especially pronounced in the following Malaria Biology areas:
Phenotypic Screening
The NF54 and K1 strains are two of the most commonly used F. plasmodium strains in labs worldwide and is used by H3D for many Malaria biology assays. Screening in both drug sensitive and resistant strains is available.
Plasmodium Single point or dose-response IC50 assays in 96-well plates
NF54: Wild-type drug-sensitive strain of P. falciparum
K1: Multidrug-resistant strain of P. falciparum
3d7: Chloroquine-sensitive strain of P. falciparum
Dd2: Chloroquine-resistant strain of P. falciparum
Mutant Resistant Strains (specialized mutants produced in-house)
KAF156-Dd2: Lab-generated mutant to in-development antimalarial KAF-156/Ganaplacide used in mechanism of action studies
PKG-3d7: Lab-generated mutant containing altered PKG enzyme used for cGMP kinase target studies
048-Dd2: Lab-generated mutant to in-development antimalarial MMV048 used in mechanism of action studies to identify PI4 kinase inhibitors
Stage Specificity
The entire malarial life cycle contains 14 stages between the human and mosquito hosts; stage-specific assessment of candidate drug inhibitory effects is necessary to clarify which symptomatic stage or stages a compound has potential for clinically relevant activity in.
PKG Enzymatic Assay: cGMP-dependent protein kinase
In vivoNSG Mouse Model
NSG/SCID studies are a highly specialized and unique set of assays in which new antiplasmodial compounds can be properly evaluated in a live model using human species of malaria. This is accomplished by using SCID (severe combined immunodeficiency) mice that have been infused with human blood, and subsequently can be studied as an experimental model of functional human malaria.
NSG/SCID studies
NSG in vivo antimalarial efficacy and PK/PD study
Dose fractionation study in vivo
Data from these assays can be used for lead optimization and drug candidate evaluation and results from these assays thereby inform key decision making and experimental design of human and/or animal in vivo studies.